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First Patient Dosed in Kymera’s Phase 2 AD Trial of KT-474


KT-474 is a first-in-class, investigational IRAK4 degrader.



Kymera Therapeutics recently announced that the first patient has been dosed in its randomized phase 2 clinical trial, ADVANTA, evaluating the safety and efficacy of KT-474 (SAR444656) for the treatment of atopic dermatitis (AD). Kymera’s collaboration with Sanofi will generate a $15 million milestone payment. ADVANTA’s evaluation of KT-474, a first-in-class, investigational IRAK4 degrader, will be compared to placebo in adult patients with moderate to severe AD.

Currently, Sanofi is conducting phase 2 KT-474 studies in both AD and hidradenitis suppurativa (HS). The first patient in the HS trial was dosed in October 2023. Study completion dates for both trials are projected in the first quarter of 2025.

Dermatology Times recently spoke to Jared Gollob, MD, the Chief Medical Officer of Kymera Therapeutics, to discuss the results of KT-474's phase 1 trial. Published in Nature Medicine under the title "IRAK4 degrader in hidradenitis suppurativa and atopic dermatitis: a phase 1 trial," this study represents the first published clinical trial utilizing a heterobifunctional targeted protein degrader. The trial demonstrated a reduction of disease-relevant inflammatory biomarkers in the blood and skin of patients, correlating with improvements in skin lesions and symptoms. Notably, the study showcased the ability of targeted protein degradation to unlock the IRAK4 pathway.

“This is the first healthy volunteer study with a heterobifunctional degrader. Also, the first study in non-oncology patients: in this case, patients with autoimmune diseases, hidradenitis suppurativa, and atopic dermatitis, which are inflammatory skin diseases,” Gollob told Dermatology Times. “We believe our data so far have pointed toward the safety of this approach of hitting IRAK4. Having a broad oral anti-inflammatory drug that can treat multiple different autoimmune diseases can be a very different value proposition from having just injectable biologics that are more focused in what part of the inflammatory pathway they're hitting.”

The safety and efficacy of KT-474 is currently being evaluated in double blind, placebo-controlled, randomized phase 2 clinical trials in adult patients with moderate to severe HS and AD. Sanofi, which is collaborating with Kymera on the development of KT-474 outside of the oncology and immune-oncology fields, is conducting the phase 2 studies.

“It's not enough just to show skin lesions are getting better. That can be very important for how patients feel and function, but also showing that you can affect even more objective measures like pain and itching, we think, is very important,” concluded Gollob.

Continue reading more about KT-474 from Gollob here.


Kymera Therapeutics announces first patient dosed in phase 2 atopic dermatitis clinical trial of KT-474 (SAR444656), a first-in-class, investigational IRAK4 degrader, generating a $15 million payment from Sanofi. News release. BioSpace. December 7, 2023. Accessed December 7, 2023. https://www.biospace.com/article/releases/kymera-therapeutics-announces-first-patient-dosed-in-phase-2-atopic-dermatitis-clinical-trial-of-kt-474-sar444656-a-first-in-class-investigational-irak4-degrader-generating-a-15-million-payment-from-sanofi/

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